HTM_MYCTU
ID HTM_MYCTU Reviewed; 241 AA.
AC P9WKL5; F2GMK5; L0T6V5; O06426; Q7D9M8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase {ECO:0000305};
DE Short=HQNO methyltransferase {ECO:0000303|PubMed:33064871};
DE Short=HQNO-MTase {ECO:0000303|PubMed:33064871};
DE EC=2.1.1.374 {ECO:0000269|PubMed:27432954, ECO:0000269|PubMed:33064871};
DE AltName: Full=Heterocyclic toxin methyltransferase {ECO:0000303|PubMed:33064871};
GN Name=htm {ECO:0000303|PubMed:33064871}; OrderedLocusNames=Rv0560c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP INDUCTION BY ANAEROBISIS, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=S-02293 Harlingen;
RX PubMed=15528667; DOI=10.1099/mic.0.27284-0;
RA Starck J., Kallenius G., Marklund B.I., Andersson D.I., Akerlund T.;
RT "Comparative proteome analysis of Mycobacterium tuberculosis grown under
RT aerobic and anaerobic conditions.";
RL Microbiology 150:3821-3829(2004).
RN [3]
RP INDUCTION BY NAPHTHOQUINONES AND FIBRATES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15644891; DOI=10.1139/w04-067;
RA Garbe T.R.;
RT "Co-induction of methyltransferase Rv0560c by naphthoquinones and fibric
RT acids suggests attenuation of isoprenoid quinone action in Mycobacterium
RT tuberculosis.";
RL Can. J. Microbiol. 50:771-778(2004).
RN [4]
RP INDUCTION BY SALICYLATE, AND OPERON STRUCTURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16175359; DOI=10.1007/s00203-005-0037-9;
RA Denkin S., Byrne S., Jie C., Zhang Y.;
RT "Gene expression profiling analysis of Mycobacterium tuberculosis genes in
RT response to salicylate.";
RL Arch. Microbiol. 184:152-157(2005).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22485172; DOI=10.1371/journal.pone.0034471;
RA Schuessler D.L., Parish T.;
RT "The promoter of Rv0560c is induced by salicylate and structurally-related
RT compounds in Mycobacterium tuberculosis.";
RL PLoS ONE 7:E34471-E34471(2012).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INDUCTION, AND
RP MUTAGENESIS OF SER-140.
RC STRAIN=H37Rv;
RX PubMed=27432954; DOI=10.1073/pnas.1606590113;
RA Warrier T., Kapilashrami K., Argyrou A., Ioerger T.R., Little D.,
RA Murphy K.C., Nandakumar M., Park S., Gold B., Mi J., Zhang T., Meiler E.,
RA Rees M., Somersan-Karakaya S., Porras-De Francisco E., Martinez-Hoyos M.,
RA Burns-Huang K., Roberts J., Ling Y., Rhee K.Y., Mendoza-Losana A., Luo M.,
RA Nathan C.F.;
RT "N-methylation of a bactericidal compound as a resistance mechanism in
RT Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E4523-E4530(2016).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=28061949; DOI=10.1016/j.tube.2016.11.001;
RA Kokoczka R., Schuessler D.L., Early J.V., Parish T.;
RT "Mycobacterium tuberculosis Rv0560c is not essential for growth in vitro or
RT in macrophages.";
RL Tuberculosis 102:3-7(2017).
RN [9]
RP FUNCTION.
RC STRAIN=H37Rv;
RX PubMed=31380295; DOI=10.3389/fcimb.2019.00251;
RA Chen C., Han X., Yan Q., Wang C., Jia L., Taj A., Zhao L., Ma Y.;
RT "The inhibitory effect of GlmU acetyltransferase inhibitor TPSA on
RT Mycobacterium tuberculosis may be affected due to its methylation by
RT methyltransferase Rv0560c.";
RL Front. Cell. Infect. Microbiol. 9:251-251(2019).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=33064871; DOI=10.1111/febs.15595;
RA Sartor P., Bock J., Hennecke U., Thierbach S., Fetzner S.;
RT "Modification of the Pseudomonas aeruginosa toxin 2-heptyl-1-
RT hydroxyquinolin-4(1H)-one and other secondary metabolites by
RT methyltransferases from mycobacteria.";
RL FEBS J. 288:2360-2376(2021).
CC -!- FUNCTION: Involved in cellular response to chemical stress and may
CC contribute to resistance toward antimicrobial natural compounds as well
CC as drugs (Probable). Catalyzes the methylation and detoxification of
CC the P.aeruginosa toxin 2-heptyl-1-hydroxy-4(1H)-quinolinone (HQNO) to
CC 2-heptyl-1-methoxy-4(1H)-quinolinone (HMOQ) (PubMed:33064871). Can also
CC methylate 3-bromo-2-heptyl-1-hydroxy-4(1H)-quinolinone, and shows much
CC lower activity with 1-hydroxyquinolin-4(1H)-one, quercetin, 4-
CC hydroxyquinolin-2(1H)-one (DHQ) and 4-hydroxyisoquinolin-1(2H)-one
CC (PubMed:33064871). In addition, N-methylates and abolishes the
CC mycobactericidal activity of 3-methyl-1-oxo-2-[3-oxo-3-(pyrrolidin-1-
CC yl)propyl]-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile
CC (compound 14), an inhibitor of DprE1 (PubMed:27432954). Also methylates
CC and reduces the inhibitory effect of TPSA (2-[5-(2-{[4-(2-thienyl)-2-
CC pyrimidinyl]sulfanyl}acetyl)-2-thienyl]acetic acid), an inhibitor of
CC GlmU acetyltransferase (PubMed:31380295). {ECO:0000269|PubMed:27432954,
CC ECO:0000269|PubMed:31380295, ECO:0000269|PubMed:33064871,
CC ECO:0000305|PubMed:33064871}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-heptyl-1-hydroxy-4(1H)-quinolinone + S-adenosyl-L-methionine
CC = 2-heptyl-1-methoxy-4(1H)-quinolinone + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:65924, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:157768,
CC ChEBI:CHEBI:157769; EC=2.1.1.374;
CC Evidence={ECO:0000269|PubMed:33064871};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65925;
CC Evidence={ECO:0000269|PubMed:33064871};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-bromo-2-heptyl-1-hydroxy-4(1H)-quinolinone + S-adenosyl-L-
CC methionine = 3-bromo-2-heptyl-1-methoxy-4(1H)-quinolinone + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:65928, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:157778,
CC ChEBI:CHEBI:157779; EC=2.1.1.374;
CC Evidence={ECO:0000269|PubMed:33064871};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65929;
CC Evidence={ECO:0000269|PubMed:33064871};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methyl-1-oxo-2-[3-oxo-3-(pyrrolidin-1-yl)propyl]-1,5-
CC dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile + S-adenosyl-
CC L-methionine = 3,5-dimethyl-1-oxo-2-[3-oxo-3-(pyrrolidin-1-
CC yl)propyl]-1,5-dihydrobenzo[4,5]imidazo[1,2-a]pyridine-4-carbonitrile
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:65932,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:158799, ChEBI:CHEBI:158993; EC=2.1.1.374;
CC Evidence={ECO:0000269|PubMed:27432954};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65933;
CC Evidence={ECO:0000269|PubMed:27432954};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.4 uM for HQNO {ECO:0000269|PubMed:33064871};
CC KM=4 uM for compound 14 {ECO:0000269|PubMed:27432954};
CC Note=kcat is 0.8 sec(-1) with HQNO as substrate (PubMed:33064871).
CC kcat is 0.074 min(-1) with compound 14 as substrate
CC (PubMed:27432954). {ECO:0000269|PubMed:27432954,
CC ECO:0000269|PubMed:33064871};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:33064871}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:A5TZU0}.
CC -!- INDUCTION: Repressed by the transcriptional repressor Rv2887
CC (PubMed:27432954). Induced by salicylate, during iron deprivation (at
CC RNA level), by anaerobiosis and by superoxide generating
CC naphthoquinones such as menadione and plumbagin and by pro-oxidant
CC phenoxyisobutyrates (fibrates) such as gemfibrozil (at protein level).
CC Part of the Rv0560c-Rv0559c operon. Operon induction is slow but is
CC maintained for at least 2 weeks in aerobic culture in the presence of
CC salicylate (PubMed:15528667, PubMed:15644891, PubMed:16175359,
CC PubMed:22485172). {ECO:0000269|PubMed:15528667,
CC ECO:0000269|PubMed:15644891, ECO:0000269|PubMed:16175359,
CC ECO:0000269|PubMed:22485172, ECO:0000269|PubMed:27432954}.
CC -!- DISRUPTION PHENOTYPE: Deletion of the gene has no effect on growth in
CC medium containing salicylate or on intra-macrophage replication
CC (PubMed:28061949). Deletion does not affect sensitivity to plumbagin,
CC menadione, nigericin, PAS or CCCP (PubMed:28061949).
CC {ECO:0000269|PubMed:28061949}.
CC -!- MISCELLANEOUS: Is dispensable under in vitro conditions in both axenic
CC and macrophage culture. {ECO:0000269|PubMed:28061949}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-17 is the initiator.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP43298.1; -; Genomic_DNA.
DR PIR; C70549; C70549.
DR RefSeq; NP_215074.1; NC_000962.3.
DR RefSeq; WP_003402938.1; NC_000962.3.
DR PDB; 7BGG; X-ray; 1.04 A; A=18-241.
DR PDB; 7NDM; X-ray; 1.35 A; A=18-241.
DR PDB; 7NMK; X-ray; 1.20 A; A=18-241.
DR PDB; 7NOY; X-ray; 1.80 A; A=18-241.
DR PDBsum; 7BGG; -.
DR PDBsum; 7NDM; -.
DR PDBsum; 7NMK; -.
DR PDBsum; 7NOY; -.
DR AlphaFoldDB; P9WKL5; -.
DR SMR; P9WKL5; -.
DR STRING; 83332.Rv0560c; -.
DR PaxDb; P9WKL5; -.
DR GeneID; 887637; -.
DR KEGG; mtu:Rv0560c; -.
DR PATRIC; fig|83332.111.peg.617; -.
DR TubercuList; Rv0560c; -.
DR eggNOG; COG2226; Bacteria.
DR OMA; EIRPARI; -.
DR PhylomeDB; P9WKL5; -.
DR BioCyc; MetaCyc:G185E-4693-MON; -.
DR BRENDA; 2.1.1.374; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0008168; F:methyltransferase activity; IBA:GO_Central.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:MTBBASE.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0001666; P:response to hypoxia; IEP:MTBBASE.
DR GO; GO:0009751; P:response to salicylic acid; IEP:MTBBASE.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR041698; Methyltransf_25.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF13649; Methyltransf_25; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..241
FT /note="2-heptyl-1-hydroxyquinolin-4(1H)-one
FT methyltransferase"
FT /id="PRO_0000419777"
FT MUTAGEN 140
FT /note="S->A: 6.7-fold increase in catalytic efficiency with
FT componud 14 as substrate."
FT /evidence="ECO:0000269|PubMed:27432954"
FT HELIX 22..30
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 94..106
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:7BGG"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:7NDM"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 146..155
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 157..169
FT /evidence="ECO:0007829|PDB:7BGG"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 183..191
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 194..206
FT /evidence="ECO:0007829|PDB:7BGG"
FT TURN 210..217
FT /evidence="ECO:0007829|PDB:7BGG"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:7BGG"
FT STRAND 229..239
FT /evidence="ECO:0007829|PDB:7BGG"
SQ SEQUENCE 241 AA; 25945 MW; 32652F8B609D5170 CRC64;
MSTVLTYIRA VDIYEHMTES LDLEFESAYR GESVAFGEGV RPPWSIGEPQ PELAALIVQG
KFRGDVLDVG CGEAAISLAL AERGHTTVGL DLSPAAVELA RHEAAKRGLA NASFEVADAS
SFTGYDGRFD TIVDSTLFHS MPVESREGYL QSIVRAAAPG ASYFVLVFDR AAIPEGPINA
VTEDELRAAV SKYWIIDEIK PARLYARFPA GFAGMPALLD IREEPNGLQS IGGWLLSAHL
G
